Photoradiation of rabbit ocular malignant melanoma sensitized with hematoporphyrin derivative

Abstract

Photoradiation therapy (PRT) against the Greene-Harvey amelanotic malignant melanoma on the rabbit iris was effectively used to cause tumor regression. A dose of 2.5 mg/kg of hematoporphyrin derivative (HPD) given intravenously, followed by photoradiation at a wavelength of 632 nm and a power density as low as 71 mW/cm² for 24 minutes (102 J/cm²) was found to be lethal for tumors 4 mm in diameter with an acceptable level of reversible toxicity to the surrounding tissues. This was best accomplished with a dye laser as the source of light because of its very narrow expanding cone of light, as emitted from a fiber optic. A 1000 Watt xenon arc lamp was also effective but not as efficient.

Because of this tumor's exceptionally rapid growth rate, it was necessary to compromise one important variable – the 3 to 4 day period between injection of HPD and photoradiation to allow for HPD depletion from normal tissues. Thus, the best tumor death responses were achieved when the light was given 1 to 16 hours after administering HPD. It is surmised that with this rapidly growing tumor, new cell progeny possess insufficient concentrations of HPD to be killed by the radiant energy. At such a short delay period, toxicity to normal tissues was observed mainly as conjunctivitis and conjunctival chemosis.

A dose level of HPD at 5 mg/kg was very close to the threshold where minor increases in light intensity would cause strong inflammatory reactions. Higher doses, at 7.5 and 10 mg/kg were excessive. A dose of 23 mg/kg accompanied by mild light energy exposures, even after 30 days, caused massive damage to normal tissues.